Background: Accelerated-chronic lymphocytic leukemia (A-CLL) is a rare disease entity as it represents less than 1% of all reported cases of chronic lymphoid leukemia (CLL). Moreover, it is most likely an under diagno...Background: Accelerated-chronic lymphocytic leukemia (A-CLL) is a rare disease entity as it represents less than 1% of all reported cases of chronic lymphoid leukemia (CLL). Moreover, it is most likely an under diagnosed entity due to its rarity and the non-standardized practice of lymph node biopsy in CLL. Purpose: The aims of our work are to establish the diagnosis of A-CLL and to study the prognosis and treatment of this rare entity. Method: here, we report the clinical presentation and the follow up of two cases of A-CLL. Results: Distinguishing Richter transformation (RT) from A-CLL is important as it may result in a major change in disease management. The prognosis of A-CLL is intermediate between CLL and RT. The prognosis is mainly poor due to a predominance of poor prognostic markers including an increasing number of p53-positive cases. Conclusion: To this date, no prospective study has been led to define the best treatment for A-CLL. The shorter survival of A-CLL when compared to typical CLL implies the need of a more aggressive treatment.展开更多
Approximately 180 million people worldwide are affected by Viral hepatitis C, with 350,000 to 500,000 deaths yearly. The present study sought to investigate the prevalence and associated factors of viral hepatitis C (...Approximately 180 million people worldwide are affected by Viral hepatitis C, with 350,000 to 500,000 deaths yearly. The present study sought to investigate the prevalence and associated factors of viral hepatitis C (VHC) among the Burundian population during a screening campaign. A total of 629 participants took part in the study, and the prevalence of viral hepatitis C was (8.11%). The associated factors identified as statistically associated were medical and surgical history (P = 0.02) and ear and nose piercing (P = 0.01). 51% of the infected persons were females. The mean age for viral hepatitis C carriage was 46.13 ± 14.3 years and 10.40% of viral hepatitis C carriers were over 50 years old. We found a high viral hepatitis C prevalence in married (9.55%) and divorced (9.38%) participants. The majority of our participants were farmers (60.25%) with a prevalence of viral hepatitis C (7.92%) while 11.54% of the infected participants were not educated. In conclusion, the current study shows a high prevalence of Viral Hepatitis C infection in Burundi. Infection was more likely to occur in older, married, farmer, and illiterates. Unsafe medical and surgical interventions with traditional practitioners were significant risk factors for contracting VHC infection.展开更多
To improve the management of patients with heart failure and anemia at the University Hospital of Brazzaville, a cross-sectional study of patients diagnosed with heart failure condition (left or global heart failure) ...To improve the management of patients with heart failure and anemia at the University Hospital of Brazzaville, a cross-sectional study of patients diagnosed with heart failure condition (left or global heart failure) was conducted over a period of nine months from January 1 to September 30, 2017. A total of 171 patients were included during the study period. Study participants were divided into two groups: Group A included patients with an additional anemic condition (n = 57) and Group NA patients without anemia (n = 114). Anemia was defined as a hemoglobin rate of < 12 g/dL for men and <11 g/dL for women. All eligible patients admitted to the Department of Cardiology were included in the study. The frequency of anemia was 33.3%, with a mean hemoglobin level of 9.4 ± 1.5 g/dL. Men accounted for 46.9% of cases (n = 79) and women 53.8% (n = 92). The mean age of eligible patients was 57.5 ± 16.5 years. Of these, 46.2% (n = 75) had a secondary educational level and 53.8% (n = 92) had a low socioeconomic status. Heart failure was global in 153 cases (89.5%). Patients were on NYHA III-IV functional class in 112 cases (65.5%), with a statistically significant difference between anemic and non-anemic patients (p = 0.0001). The main underlying heart diseases were dilated cardiomyopathy (75.1%), hypertensive heart disease (10.5%), ischemic heart disease (6.5%), and valvular disease (4.7%). The comparison between the two groups (A and NA) showed a longer hospital length of stay (18.4 ± 8.9 versus 12.9 ± 7.6 days;p = 0.00001) and a higher mortality rate (4 versus 2 deaths). The re-hospitalization rate was more important in group A (n = 4) than in group NA (n = 1). Anemia is a common condition in patients with heart failure. It worsens the clinical features and prognosis.展开更多
Introduction: Induction therapy followed by high-dose chemotherapy with autologous stem cell transplantation remains the gold standard for myeloma patients who can tolerate this treatment approach. In a developing cou...Introduction: Induction therapy followed by high-dose chemotherapy with autologous stem cell transplantation remains the gold standard for myeloma patients who can tolerate this treatment approach. In a developing country setting, in the absence of availability of bone marrow transplantation, the CTD protocol is an accessible treatment regimen whose efficacy and lower toxicity compared to the Melphalan Prednisone protocol has been reported. This protocol has been administered since 2018 in first line. It’s against this backdrop we perform this study to assess the efficacy of this CTD protocol in first line therapy. Methods: We conducted a descriptive and analytical study including clinical, paraclinical and evolutionary data of 50 patients with MM treated during the period range from 01 September 2018 and 01 July 2022 with the CTD protocol of cyclophosphamide (500 mg at D1, D8 and D15), dexamethasone (40 mg weekly) and thalidomide (100 mg/day) in 28-day cycles. Survival outcomes were estimated by the Kaplan-Meier method. Results: The mean age was 62.3 ± 9.1 years and the sex ratio was 0.7. An advanced prognostic score at diagnosis was found in 73.5% of patients according to the Salmon and Durie score and in 32% according to the ISS. Overall remission was noted in 64%, of which 34% were in very good partial remission and partial remission in 12% of cases. Progression was noted in 4 patients. Treatment-related side effects were mainly peripheral neuropathy and anaemia in 3 patients respectively. The median survival was 38.4 months. The progression-free survival was 60%. An advanced age (≥65 years) is correlated with negative impact on survival (p = 0.04). Conclusion: Cyclophosphamide, thalidomide and dexamethasone give good outcome with less toxicity. Thus, it remains a first-line treatment alternative for newly diagnosed and low-income patients.展开更多
To contribute to improving the management of patients with heart failure and anemia in Brazzaville, a prospective and descriptive study was conducted in the University Hospital of Brazzaville for nine months (January ...To contribute to improving the management of patients with heart failure and anemia in Brazzaville, a prospective and descriptive study was conducted in the University Hospital of Brazzaville for nine months (January 1st to September 30, 2017). Included 57 patients hospitalized for left or global heart failure and presenting anemia. Anemia was defined by an haemoglobin level < 12 g/dL in men and <11 g/dL in women. Proportionings of the reticulocytes rate, serum iron, ferritin, erythrocyte sedimentation rate (ESR) and/or C-reactive protein (CRP), electrophoresis of proteins, and evaluation of renal function by glomerular filtration rate (GFR), as well as the treatments of heart failure, and the auxiliary therapeutic ones, in particular the antithrombotic drugs, allowed aetiologic research. They were 20 men (35%) and 37 women (65%), old on average of 59 ± 17 years. The average rate of haemoglobin was 11.4 ± 1.4 g/dL. Heart failure was de novo in 24 cases (42.1%), old in 33 cases (57.9%);it was global in 54 cases (94.7%).The maintenance treatment associated diuretics in 32 cases (97%), angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) in 31 cases (94%), beta-blockers in two cases (6.1%), digoxin in four cases (12.1%), aspirin in five cases (15.1%) and anti-vitamin K in four cases (12.1%). Anemia was microcytic hypochromic in 30 cases (52.6%), normocytic normochromic in 20 cases (35.1%), and macrocytic normochromic in one case (1.7%). The main aetiologic factors were hemodilution in 46 cases (80.7%), renal insufficiency in 30 cases (52.3%), inflammation in 29 cases (50.8%), and iron deficiency in one case (1.7%). The HIV serology, carried out in 11 cases, was negative. Anemia is a frequent comorbidity among heart failure patients. Aetiologic research remains difficult in our context, and its often multifactorial origin.展开更多
Monoclonal antibodies(MAbs) are important tools for the study of proteins′ function and structure. But there has been no report on the preparation of MAbs against human KIAA0100 protein up to date. Here, first, we ge...Monoclonal antibodies(MAbs) are important tools for the study of proteins′ function and structure. But there has been no report on the preparation of MAbs against human KIAA0100 protein up to date. Here, first, we generated the mouse MAb against human KIAA0100 protein using purified recombinant 6×Histidinc(6×His)-tagged human KIAA0100 protein segment(1557–2234) as an antigen; then, the m RNA expression of human KIAA0100 gene was detected in U937 cells using Northern blot analysis. The results showed that the mouse MAb against human KIAA0100 protein could sensitively recognize the human KIAA0100 protein using Western blot analysis and immunocytochemistry analysis. Besides, Western blot analysis revealed that human KIAA0100 gene possibly encoded two different protein products(254 k Da and < 250 k Da) in U937 cells. Moreover,Northern blot analysis confirmed that human KIAA0100 gene might produced two different m RNA products(6000–10000 bp and 5000–6000 bp) in U937 cells. The results provide a basis for large-scale production of the MAb against human KIAA0100 protein, which will be useful for the study of human KIAA0100 protein′s function/structure and MAb-targeted drugs in the future.展开更多
MANY cases of pure red cell aplasia （PRCA） were mediated by over-function of immune cells, and responded well to immunosuppressive therapy. Sometimes refractory cases also arose. Fludarabine is an analogue of adenos...MANY cases of pure red cell aplasia （PRCA） were mediated by over-function of immune cells, and responded well to immunosuppressive therapy. Sometimes refractory cases also arose. Fludarabine is an analogue of adenosine resistant to deamination which is widely used for B-chronic lymphocytic leukemia （CLL） and other hematological malignancies.^2 As a strong immunosuppressive agent, fludarabine has generally been used in nonmyeloblative conditioning regimens for hematopoietic stem cells transplantation for hematological malignancies and severe aplastic anemia recently.^3 In this study,展开更多
Our previous study demonstrated that human KIAA0100 gene was a novel acute monocytic leukemia-associated antigen (MLAA) gene. But the functional characterization of human KIAA0100 gene has remained unknown to date. He...Our previous study demonstrated that human KIAA0100 gene was a novel acute monocytic leukemia-associated antigen (MLAA) gene. But the functional characterization of human KIAA0100 gene has remained unknown to date. Here, firstly, bioinformatic prediction of human KIAA0100 gene was carried out using online softwares; Secondly, Human KIAA0100 gene expression was downregulated by the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) 9 system in U937 cells. Cell proliferation and apoptosis were next evaluated in KIAA0100-knockdown U937 cells. The bioinformatic prediction showed that human KIAA0100 gene was located on 17q11.2, and human KIAA0100 protein was located in the secretory pathway. Besides, human KIAA0100 protein contained a signalpeptide, a transmembrane region, three types of secondary structures (alpha helix, extended strand, and random coil) , and four domains from mitochondrial protein 27 (FMP27). The observation on functional characterization of human KIAA0100 gene revealed that its downregulation inhibited cell proliferation, and promoted cell apoptosis in U937 cells. To summarize, these results suggest human KIAA0100 gene possibly comes within mitochondrial genome; moreover, it is a novel anti-apoptotic factor related to carcinogenesis or progression in acute monocytic leukemia, and may be a potential target for immunotherapy against acute monocytic leukemia.展开更多
Objective: To study the therapeutic potential of Fas inhibition in different diseases, a Fas-targeting siRNA (small interfering)-expressing plasmid was constructed. Methods: The U6 promoter cassette and siFas (small i...Objective: To study the therapeutic potential of Fas inhibition in different diseases, a Fas-targeting siRNA (small interfering)-expressing plasmid was constructed. Methods: The U6 promoter cassette and siFas (small interfering RNA that inhibit Fas expression) template sequence were obtained by PCR method. They were cloned into modified pcDNA3.1. The resultant plasmid pU6-siFas was transfected into P815 cells with lipofectin2000 and selected under G-418-containing culture medium. Fas inhibition in stably transfected cells was detected by immunocytochemistry. Results: The plasmid pU6-siFas efficiently reduced the expression of Fas and conferred G-418 resistance in P815 cells. Conclusion: The successful construction of the siRNA expressing plasmid will facilitate the application of RNA interference technique and lay the foundation for further study of Fas inhibition in the treatment of different diseases such as aplastic anemia and acute liver failure.展开更多
The European Clinical Laboratory and Molecular(ECLM) criteria define 10 distinct Willebrand diseases(VWD) recessive type 3, severe 1, 2C and 2N; dominant VWD type 1 secretion/clearance defect, 2A, 2B, 2E, 2M and 2D; ...The European Clinical Laboratory and Molecular(ECLM) criteria define 10 distinct Willebrand diseases(VWD) recessive type 3, severe 1, 2C and 2N; dominant VWD type 1 secretion/clearance defect, 2A, 2B, 2E, 2M and 2D; and mild type 1 VWD(usually carriers of recessive VWD). Recessive severe 1 and 2C VWD are characterized by secretion and multimerization defects caused by mutations in the D1-D2 domain. Recessive 2N VWD is a mild hemophilia due to D'-FVIII-von Willebrand factor(VWF) binding site mutations. Dominant 2E VWD caused by heterozygous missense mutations in the D3 domain is featured by a secretion-clearancemultimerization VWF defect. Dominant VWD type 2M due to loss of function mutations in the A1 domain is characterized by decreased ristocetin-induced platelet aggregation and VWF RCo, normal VWF multimers and VWF CB, a poor response of VWF RCo and good response of VWF CB to desmopressin(DDAVP). Dominant VWD type 2A induced by heterozygous mutations in the A2 domain results in hypersensitivity of VWF for proteolysis by ADAMTS13 into VWF degradationproducts, resulting in loss of large VWF multimers with triplet structure of each individual VWF band. Dominant VWD type 2B due to a gain of function mutation in the A1 domain is featured by spontaneous interaction between platelet glycoprotein Ib(GPIb) and mutated VWF A1 followed by increased proteolysis with loss of large VWF multimers and presence of each VWF band. A new category of dominant VWD type 1 secretion or clearance defect due to mutations in the D3 domain or D4-C1-C5 domains consists of two groups Those with normal or smeary pattern of VWF multimers.展开更多
Objective The whole process of vaccine preparation is time-consuming and technically challenging. Here the hGM-CSF-engineered K-562 cell line was constructed to simplify tumor vaccine preparation process. Methods The ...Objective The whole process of vaccine preparation is time-consuming and technically challenging. Here the hGM-CSF-engineered K-562 cell line was constructed to simplify tumor vaccine preparation process. Methods The eukaryocyte expressing plasmid pcDNA3.1/GM-CSF was first constructed and its accuracy was verified through sequencing. The pcDNA3.1/GM-CSF was transfected into COS-7 cells to verify GM-CSF expression and cytokine activity using TF-1 cell line. Then the plasmid was transfected into K-562 cell line using liposome method, and was selected under G-418 and sub-cloned by limiting dilution. GM-CSF product from the monoclone GM-CSF-K-562 cell lines was quantified using ELISA method. Results We successfully constructed the hGM-CSF eukaryocyte expressing plasmid and hGM-CSF expressing K-562 cell line. Conclusion The construction of K-562/GM-CSF line will simplify the preparation of tumor vaccine, thus facilitating the application of tumor vaccination therapy in clinical application.展开更多
The CD4+/CD56+ hematodermic neoplasm is a rare aggressive systemic neoplasm for which effective therapies have not yet been established, it is clinically characterized by cutaneous involvement with spread to bone marr...The CD4+/CD56+ hematodermic neoplasm is a rare aggressive systemic neoplasm for which effective therapies have not yet been established, it is clinically characterized by cutaneous involvement with spread to bone marrow, blood and poor prognosis with current chemotherapy regimens. Our objective is to report diagnosis and treatment difficulties of CD4+/CD56+ hematodermic neoplasm. We describe here a Tunisian man who presented with subcutaneous ulcerated lesion localized in the right leg and multiples generalized nodules. Skin biopsy showed an atypical lymphoid cell infiltration with an angiocentric pattern and extensive necrosis by immuno-histochemical analysis, these cells were positive for CD4, CD56, granzyme B and negative for CD8, CD123, CD20 and CD30. T-cell rearrangement and Epstein-Barr-virus (EBV) in situ hybridation studies were negative. The patient underwent 5 cycles chemotherapy SMILE regimen monthly sandwiched with radiotherapy on the residual lesions of the right leg with great tolerance but he relapsed within 8months with skin, blood, bone marrow, lung, and cerebrospinal involvement. Based on these findings, the patient was diagnosed with CD4+/CD56+ hematodermic neoplasm (blastic NK-like T-cell lymphoma) treated with one course of hyper-CVAD regimen, he died within 20 days with a septic chok. Despite the use of L-Asparaginase and radiotherapy the prognosis is very poor;we suggest the exploration for highly active drugs, hematopoietic stem cell transplantation (HSCT) is crucial to improve survival.展开更多
Sickle cell disease is an autosomal recessive genetic disease. Vaso occlusive crisis (VOC) is frequently seen in such patients. Painful VOC is usually recurrent, of variable severity due to many factors and its manage...Sickle cell disease is an autosomal recessive genetic disease. Vaso occlusive crisis (VOC) is frequently seen in such patients. Painful VOC is usually recurrent, of variable severity due to many factors and its management poses important challenge in the clinical practice. Few patients do not respond to standard therapies and continue to suffer severe pain for prolonged period or land to serious life threatening situation. The red cell exchange by aphaeresis is presumed to be one efficient alternative in this situation which can reduce the level of HbS below 40% - 50%. However, it is costly and not available everywhere. Both circumstances are common in our state where incidence of sickle cell disease is quite high. In such situations simple red cell exchange i.e. removing 1 unit (350 ml) of blood manually (by phlebotomy) and replacement with one unit normal red cell is effective. All of our four cases of SCA with severe acute VOC, are not responding to standard therapy but responded efficiently to this simple red cell exchange transfusion. Our present observation may pave the way of one simple, affordable, and effective measure to reduce the pain of severe acute VOC not responding to standard therapy. Moderate reduction of HbS by 8% - 14% by simple red cell exchange transfusion was associated with relief of pain of acute VOC;a new observation was reported in all our 4 cases which need to be validated by larger controlled studies.展开更多
Background and Aim: Primary testicular lymphoma (PTL) is a rare form of extranodal non-Hodgkin’s lymphoma. It represents for 1% - 2% of non-Hodgkin’s lymphoma, and mostly affects the elderly. We describe an int...Background and Aim: Primary testicular lymphoma (PTL) is a rare form of extranodal non-Hodgkin’s lymphoma. It represents for 1% - 2% of non-Hodgkin’s lymphoma, and mostly affects the elderly. We describe an interesting case of PTL managed by a combined multimodal approach with a review of the literature. Case Presentation: Patient aged 56 years, consulted for an increase in the volume of the right testicle without associated pain, all evolving in the context of a slight decline in general condition. Clinical examination revealed a large painless mass in the right scrotal bursa. A scrotal ultrasound showed a right intra-testicular mass. The patient had undergone inguinal orchiectomy. Pathological analysis showed diffuse large B-cell lymphoma of the testis. Whole-body 18-fluorodeoxyglucose positron emission tomography (18-FDG-PET-CT) showed no suspicious hypermetabolism. Lumbar puncture did not reveal malignant cells in the cerebrospinal fluid (CSF). The patient then received 6 cycles of chemotherapy according to the R-CHOP protocol (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone) and 2 cycles of intrathecal methotrexate. After chemotherapy, scrotal radiotherapy at a dose of 30 Gy was delivered. The evolution was marked by the death of the patient six months after the end of the scrotal radiotherapy following a diffuse lymph node relapse with a profound alteration of the general state. Conclusion: The treatment depends imperatively on the stage of the disease. The therapeutic approach is multimodal and combined based on orchiectomy, systemic and intrathecal treatment and scrotal radiotherapy. PTL is an aggressive malignant with a poor prognosis. Randomized trials are needed to define a better therapeutic strategy.展开更多
Objective:To evaluate coagulation abnormalities and their relationship with bleeding manifestations among patients with dengue.Methods:This observational study was conducted on 292 adult dengue patients who were admit...Objective:To evaluate coagulation abnormalities and their relationship with bleeding manifestations among patients with dengue.Methods:This observational study was conducted on 292 adult dengue patients who were admitted to a tertiary care hospital of Western India from July 2021 to June 2022.Coagulation tests including prothrombin time(PT),international normalized ratio(INR),activated partial thromboplastin time(aPTT),fibrinogen,and D-dimer were performed.Patients were monitored for bleeding manifestations.Results:Coagulation abnormalities were reported in 42.8%of the patients.Overall,prolonged aPTT was the most common coagulation abnormality(40.8%),followed by low fibrinogen(38.7%),raised D-dimer(31.2%),raised INR(26.0%)and prolonged PT(19.2%).Bleeding manifestations were present in 19.9%patients.PT,INR,aPTT and D-dimer levels were significantly higher(P<0.01)and fibrinogen level was significantly lower(P<0.001)in patients with bleeding compared to patients without bleeding.Patients with bleeding had a significantly higher rate of all coagulation abnormalities than patients without bleeding(P<0.01).Conclusions:Patients with bleeding showed a significantly higher frequency of coagulation abnormalities compared to patients without bleeding.Patients with dengue should be assessed for coagulation abnormalities.展开更多
AIM: To assess the effect of Helicobacter pylori (H. pylori) eradication on platelet counts in patients with chronic immune thrombocytopenic purpura (cITP).
The acquisition of secondary chromosomal aberrations in chronic myeloid leukemia (CML) patients with Philadelphia chromosome-positive (Ph+) karyotype signifies clonal evolution associated with the progression of the d...The acquisition of secondary chromosomal aberrations in chronic myeloid leukemia (CML) patients with Philadelphia chromosome-positive (Ph+) karyotype signifies clonal evolution associated with the progression of the disease to its accelerated or blastic phase. Therefore, these aberrations have clinical and biological significance. T(3;12)(q26;p13), which is a recurrent chromosomal aberration observed in myeloid malignancies, is typically associated with dysplasia of megakaryocytes, multilineage involvement, short duration of any blastic phase, and extremely poor prognosis. We have identified a recurrent reciprocal translocation between chromosomes 3 and 12 with different breakpoint at bands 3q21 in the malignant cells from a 28-year-old man. The patient was initially diagnosed as having Ph+ CML in the chronic phase. The t(3;12)(q21;p13) translocation occurred 4 years after the patient was first diagnosed with CML while undergoing tyrosine kinase inhibitor therapy. We confirmed the t(3;12)(q21;p13) translocation via fluorescence in situ hybridization assay by using whole-chromosome paint probes for chromosomes 3 and 12. Our findings demonstrate that, similar to other recurrent translocations involving 3q26 such as t(3;3) and t(3;21), the t(3;12)(q21;p13) translocation is implicated not only in myelodysplastic syndrome and acute myeloid leukemia but also in the progression of CML. These findings extend the disease spectrum of this cytogenetic aberration.展开更多
Dasatinib is a second-line tyrosine kinase inhibitor used in patients with imatinib resistant or intolerant chronic myeloid leukemia (CML) and Philadelphia chromosomepositive acute leukemia. Gastrointestinal bleeding ...Dasatinib is a second-line tyrosine kinase inhibitor used in patients with imatinib resistant or intolerant chronic myeloid leukemia (CML) and Philadelphia chromosomepositive acute leukemia. Gastrointestinal bleeding may occur in up to 7% of patients using dasatinib, although, severe dasatinib-related acute colitis had rarely been reported. Here, we present the case of a 36-year-old female who progressed to acute myeloid leukemia after fourteen months of receiving imatinib for CML in the chronic phase and was treated with a dasatinib-containing chemotherapy regimen. On day 34 of treatment, the patient developed moderate abdominal pain and bloody diarrhea with mucous. Analyses of stool specimens were negative for parasites, Clostridium difficile , and other pathogenic bacteria. The cytomegalovirus pp65 antigen was negative in her blood leukocytes. A colonoscopy revealed acute colitis, and a mucosal biopsy showed nonspecific colitis. The patient was treated with broad-spectrum antibiotics, bowel rest and hydration, and dasatinib treatment was stopped. Her bloody diarrhea improved within 72 h. After confirming cytological remission, the patient received initial course of consolidation, and dasatinib treatment was reinstated. However, hemorrhagic colitis recurred. After discontinuing dasatinib, herhemorrhagic colitis drastically improved and did not recur following the administration of nilotinib. The characteristics of our patient suggest that dasatinib treatment can lead to hemorrhagic colitis, which typically resolves after discontinuation of the drug.展开更多
Background: The role of human multidrug resistance gene (MDR1) SNPs in the interindividual variability of imatinib mesylate (IM) response has received considerable attention. We aimed to study the association between ...Background: The role of human multidrug resistance gene (MDR1) SNPs in the interindividual variability of imatinib mesylate (IM) response has received considerable attention. We aimed to study the association between SNPs of the MDR1 gene (C1236T, G2677T/A, C3435T) and IM response in chronic myeloid leukemia (CML) patients. Method: A retrospective case-control study was conducted on 48 patients with CML undergoing IM therapy. All patients were genotyped using PCR-RFLP method. Results: The genotype and allele frequencies of C1236T and C3435T were not significantly different between CML patients responders and non-responders to IM (p > 0.05). The frequencies of 2677T allele and 2677TT genotype were significantly increased in CML patients IM responders which as compared with IM non-responders (50% vs 26.9%, p = 0.013 and 27.3% vs 3.8%, p = 0.029 respectively). Whereas the 2677AA genotype and CAC haplotype were found only in CML patients IM non-responders (15.4%). Conclusion: Pretreatment genotyping of G2677A/T appears to be useful for predicting IM resistance, which may allow the best choice of drug treatment for CML patients.展开更多
Background Myelodysplastic syndromes (MDSs), also called preleukemias, are a group of myeloid hematopoietic malignant disorders. We studied the transformation of MDS into acute myeloid leukemia (AML).Methods Leukemi...Background Myelodysplastic syndromes (MDSs), also called preleukemias, are a group of myeloid hematopoietic malignant disorders. We studied the transformation of MDS into acute myeloid leukemia (AML).Methods Leukemic transformation in 151 patients with MDS was dynamically followed up. The clinical manifestation, peripheral blood and bone marrow condition, karyotypes, immunophenotypes, response to treatment, and prognosis of AML evolution from MDS (MDS-AML) were also observed.Results During the course of this study, over the past eight years and seven months, 21 (13.91%) of 151 MDS patients progressed to overt leukemia, with a median interval of 5 (1-23) months. There were no significant differences between rates of leukemic transformation in comparison with the refractory anemia (RA), RA with excess of blasts (RAEB), and RAEB in transformation (RAEB-t) patient groups. Transformation occurred either gradually or rapidly. There were five parameters positively correlated to leukemic transformation: under 40 years of age, pancytopenia of 3 lineages, more than 15% blasts in the bone marrow, at least two abnormal karyotypes, and treatment with combined chemotherapy. All of the 21 patients with leukemia suffered from MDS-AML, and most of them were M 2, M 4, or M 5. Two (9.52%) MDS-AML patients developed extramedullary infiltration. Leukopenia was found in 47.62% of these patients. Two thirds of these patients, whose bone marrows were generally hypercellular, suffered from neutropenia. After developing AML, 8 (47.06%) patients developed abnormal karyotypes. High expression of immature myeloid antigens, including CD 33 [(49.83±24.50)%], CD 13 [(36.38±33.84)%], monocytic antigen CD 14 [(38.50±24.60)%], and stem cell marker CD 34 [(34.67±30.59)%], were found on bone marrow mononuclear cells from MDS-AML patients after leukemic transformation. In some cases, lymphoid antigens, such as CD 5, CD 7, CD 9, and CD 19, coexisted with myeloid antigens. A low complete remission rate (31.25%) and a short survival time, with median survival of 6 (1-28) months, were found in patients with MDS-AML treated by induction chemotherapy.Conclusions MDS has a high risk of developing into AML, either gradually or rapidly. Patients with MDS-AML have specific biological characteristics and a worse prognosis.展开更多
文摘Background: Accelerated-chronic lymphocytic leukemia (A-CLL) is a rare disease entity as it represents less than 1% of all reported cases of chronic lymphoid leukemia (CLL). Moreover, it is most likely an under diagnosed entity due to its rarity and the non-standardized practice of lymph node biopsy in CLL. Purpose: The aims of our work are to establish the diagnosis of A-CLL and to study the prognosis and treatment of this rare entity. Method: here, we report the clinical presentation and the follow up of two cases of A-CLL. Results: Distinguishing Richter transformation (RT) from A-CLL is important as it may result in a major change in disease management. The prognosis of A-CLL is intermediate between CLL and RT. The prognosis is mainly poor due to a predominance of poor prognostic markers including an increasing number of p53-positive cases. Conclusion: To this date, no prospective study has been led to define the best treatment for A-CLL. The shorter survival of A-CLL when compared to typical CLL implies the need of a more aggressive treatment.
文摘Approximately 180 million people worldwide are affected by Viral hepatitis C, with 350,000 to 500,000 deaths yearly. The present study sought to investigate the prevalence and associated factors of viral hepatitis C (VHC) among the Burundian population during a screening campaign. A total of 629 participants took part in the study, and the prevalence of viral hepatitis C was (8.11%). The associated factors identified as statistically associated were medical and surgical history (P = 0.02) and ear and nose piercing (P = 0.01). 51% of the infected persons were females. The mean age for viral hepatitis C carriage was 46.13 ± 14.3 years and 10.40% of viral hepatitis C carriers were over 50 years old. We found a high viral hepatitis C prevalence in married (9.55%) and divorced (9.38%) participants. The majority of our participants were farmers (60.25%) with a prevalence of viral hepatitis C (7.92%) while 11.54% of the infected participants were not educated. In conclusion, the current study shows a high prevalence of Viral Hepatitis C infection in Burundi. Infection was more likely to occur in older, married, farmer, and illiterates. Unsafe medical and surgical interventions with traditional practitioners were significant risk factors for contracting VHC infection.
文摘To improve the management of patients with heart failure and anemia at the University Hospital of Brazzaville, a cross-sectional study of patients diagnosed with heart failure condition (left or global heart failure) was conducted over a period of nine months from January 1 to September 30, 2017. A total of 171 patients were included during the study period. Study participants were divided into two groups: Group A included patients with an additional anemic condition (n = 57) and Group NA patients without anemia (n = 114). Anemia was defined as a hemoglobin rate of < 12 g/dL for men and <11 g/dL for women. All eligible patients admitted to the Department of Cardiology were included in the study. The frequency of anemia was 33.3%, with a mean hemoglobin level of 9.4 ± 1.5 g/dL. Men accounted for 46.9% of cases (n = 79) and women 53.8% (n = 92). The mean age of eligible patients was 57.5 ± 16.5 years. Of these, 46.2% (n = 75) had a secondary educational level and 53.8% (n = 92) had a low socioeconomic status. Heart failure was global in 153 cases (89.5%). Patients were on NYHA III-IV functional class in 112 cases (65.5%), with a statistically significant difference between anemic and non-anemic patients (p = 0.0001). The main underlying heart diseases were dilated cardiomyopathy (75.1%), hypertensive heart disease (10.5%), ischemic heart disease (6.5%), and valvular disease (4.7%). The comparison between the two groups (A and NA) showed a longer hospital length of stay (18.4 ± 8.9 versus 12.9 ± 7.6 days;p = 0.00001) and a higher mortality rate (4 versus 2 deaths). The re-hospitalization rate was more important in group A (n = 4) than in group NA (n = 1). Anemia is a common condition in patients with heart failure. It worsens the clinical features and prognosis.
文摘Introduction: Induction therapy followed by high-dose chemotherapy with autologous stem cell transplantation remains the gold standard for myeloma patients who can tolerate this treatment approach. In a developing country setting, in the absence of availability of bone marrow transplantation, the CTD protocol is an accessible treatment regimen whose efficacy and lower toxicity compared to the Melphalan Prednisone protocol has been reported. This protocol has been administered since 2018 in first line. It’s against this backdrop we perform this study to assess the efficacy of this CTD protocol in first line therapy. Methods: We conducted a descriptive and analytical study including clinical, paraclinical and evolutionary data of 50 patients with MM treated during the period range from 01 September 2018 and 01 July 2022 with the CTD protocol of cyclophosphamide (500 mg at D1, D8 and D15), dexamethasone (40 mg weekly) and thalidomide (100 mg/day) in 28-day cycles. Survival outcomes were estimated by the Kaplan-Meier method. Results: The mean age was 62.3 ± 9.1 years and the sex ratio was 0.7. An advanced prognostic score at diagnosis was found in 73.5% of patients according to the Salmon and Durie score and in 32% according to the ISS. Overall remission was noted in 64%, of which 34% were in very good partial remission and partial remission in 12% of cases. Progression was noted in 4 patients. Treatment-related side effects were mainly peripheral neuropathy and anaemia in 3 patients respectively. The median survival was 38.4 months. The progression-free survival was 60%. An advanced age (≥65 years) is correlated with negative impact on survival (p = 0.04). Conclusion: Cyclophosphamide, thalidomide and dexamethasone give good outcome with less toxicity. Thus, it remains a first-line treatment alternative for newly diagnosed and low-income patients.
文摘To contribute to improving the management of patients with heart failure and anemia in Brazzaville, a prospective and descriptive study was conducted in the University Hospital of Brazzaville for nine months (January 1st to September 30, 2017). Included 57 patients hospitalized for left or global heart failure and presenting anemia. Anemia was defined by an haemoglobin level < 12 g/dL in men and <11 g/dL in women. Proportionings of the reticulocytes rate, serum iron, ferritin, erythrocyte sedimentation rate (ESR) and/or C-reactive protein (CRP), electrophoresis of proteins, and evaluation of renal function by glomerular filtration rate (GFR), as well as the treatments of heart failure, and the auxiliary therapeutic ones, in particular the antithrombotic drugs, allowed aetiologic research. They were 20 men (35%) and 37 women (65%), old on average of 59 ± 17 years. The average rate of haemoglobin was 11.4 ± 1.4 g/dL. Heart failure was de novo in 24 cases (42.1%), old in 33 cases (57.9%);it was global in 54 cases (94.7%).The maintenance treatment associated diuretics in 32 cases (97%), angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) in 31 cases (94%), beta-blockers in two cases (6.1%), digoxin in four cases (12.1%), aspirin in five cases (15.1%) and anti-vitamin K in four cases (12.1%). Anemia was microcytic hypochromic in 30 cases (52.6%), normocytic normochromic in 20 cases (35.1%), and macrocytic normochromic in one case (1.7%). The main aetiologic factors were hemodilution in 46 cases (80.7%), renal insufficiency in 30 cases (52.3%), inflammation in 29 cases (50.8%), and iron deficiency in one case (1.7%). The HIV serology, carried out in 11 cases, was negative. Anemia is a frequent comorbidity among heart failure patients. Aetiologic research remains difficult in our context, and its often multifactorial origin.
基金financial support from the National Natural Science Foundation of China (81270596)
文摘Monoclonal antibodies(MAbs) are important tools for the study of proteins′ function and structure. But there has been no report on the preparation of MAbs against human KIAA0100 protein up to date. Here, first, we generated the mouse MAb against human KIAA0100 protein using purified recombinant 6×Histidinc(6×His)-tagged human KIAA0100 protein segment(1557–2234) as an antigen; then, the m RNA expression of human KIAA0100 gene was detected in U937 cells using Northern blot analysis. The results showed that the mouse MAb against human KIAA0100 protein could sensitively recognize the human KIAA0100 protein using Western blot analysis and immunocytochemistry analysis. Besides, Western blot analysis revealed that human KIAA0100 gene possibly encoded two different protein products(254 k Da and < 250 k Da) in U937 cells. Moreover,Northern blot analysis confirmed that human KIAA0100 gene might produced two different m RNA products(6000–10000 bp and 5000–6000 bp) in U937 cells. The results provide a basis for large-scale production of the MAb against human KIAA0100 protein, which will be useful for the study of human KIAA0100 protein′s function/structure and MAb-targeted drugs in the future.
基金Supported by the Natural Science Foundation of Jiangsu Province(2004BK424)the 135 Key Department Fund of Jiangsu Province(135XY0416)the Outstanding Person Fund of the First Affiliated Hospital of Soochow University(2004YQG05)
文摘MANY cases of pure red cell aplasia （PRCA） were mediated by over-function of immune cells, and responded well to immunosuppressive therapy. Sometimes refractory cases also arose. Fludarabine is an analogue of adenosine resistant to deamination which is widely used for B-chronic lymphocytic leukemia （CLL） and other hematological malignancies.^2 As a strong immunosuppressive agent, fludarabine has generally been used in nonmyeloblative conditioning regimens for hematopoietic stem cells transplantation for hematological malignancies and severe aplastic anemia recently.^3 In this study,
基金financial support from the National Natural Science Foundation of China (No. 081718110232)
文摘Our previous study demonstrated that human KIAA0100 gene was a novel acute monocytic leukemia-associated antigen (MLAA) gene. But the functional characterization of human KIAA0100 gene has remained unknown to date. Here, firstly, bioinformatic prediction of human KIAA0100 gene was carried out using online softwares; Secondly, Human KIAA0100 gene expression was downregulated by the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) 9 system in U937 cells. Cell proliferation and apoptosis were next evaluated in KIAA0100-knockdown U937 cells. The bioinformatic prediction showed that human KIAA0100 gene was located on 17q11.2, and human KIAA0100 protein was located in the secretory pathway. Besides, human KIAA0100 protein contained a signalpeptide, a transmembrane region, three types of secondary structures (alpha helix, extended strand, and random coil) , and four domains from mitochondrial protein 27 (FMP27). The observation on functional characterization of human KIAA0100 gene revealed that its downregulation inhibited cell proliferation, and promoted cell apoptosis in U937 cells. To summarize, these results suggest human KIAA0100 gene possibly comes within mitochondrial genome; moreover, it is a novel anti-apoptotic factor related to carcinogenesis or progression in acute monocytic leukemia, and may be a potential target for immunotherapy against acute monocytic leukemia.
基金Project (No. 20012131) supported by the National Administer of Health-supported Clinical Department Developing Funding, China
文摘Objective: To study the therapeutic potential of Fas inhibition in different diseases, a Fas-targeting siRNA (small interfering)-expressing plasmid was constructed. Methods: The U6 promoter cassette and siFas (small interfering RNA that inhibit Fas expression) template sequence were obtained by PCR method. They were cloned into modified pcDNA3.1. The resultant plasmid pU6-siFas was transfected into P815 cells with lipofectin2000 and selected under G-418-containing culture medium. Fas inhibition in stably transfected cells was detected by immunocytochemistry. Results: The plasmid pU6-siFas efficiently reduced the expression of Fas and conferred G-418 resistance in P815 cells. Conclusion: The successful construction of the siRNA expressing plasmid will facilitate the application of RNA interference technique and lay the foundation for further study of Fas inhibition in the treatment of different diseases such as aplastic anemia and acute liver failure.
文摘The European Clinical Laboratory and Molecular(ECLM) criteria define 10 distinct Willebrand diseases(VWD) recessive type 3, severe 1, 2C and 2N; dominant VWD type 1 secretion/clearance defect, 2A, 2B, 2E, 2M and 2D; and mild type 1 VWD(usually carriers of recessive VWD). Recessive severe 1 and 2C VWD are characterized by secretion and multimerization defects caused by mutations in the D1-D2 domain. Recessive 2N VWD is a mild hemophilia due to D'-FVIII-von Willebrand factor(VWF) binding site mutations. Dominant 2E VWD caused by heterozygous missense mutations in the D3 domain is featured by a secretion-clearancemultimerization VWF defect. Dominant VWD type 2M due to loss of function mutations in the A1 domain is characterized by decreased ristocetin-induced platelet aggregation and VWF RCo, normal VWF multimers and VWF CB, a poor response of VWF RCo and good response of VWF CB to desmopressin(DDAVP). Dominant VWD type 2A induced by heterozygous mutations in the A2 domain results in hypersensitivity of VWF for proteolysis by ADAMTS13 into VWF degradationproducts, resulting in loss of large VWF multimers with triplet structure of each individual VWF band. Dominant VWD type 2B due to a gain of function mutation in the A1 domain is featured by spontaneous interaction between platelet glycoprotein Ib(GPIb) and mutated VWF A1 followed by increased proteolysis with loss of large VWF multimers and presence of each VWF band. A new category of dominant VWD type 1 secretion or clearance defect due to mutations in the D3 domain or D4-C1-C5 domains consists of two groups Those with normal or smeary pattern of VWF multimers.
文摘Objective The whole process of vaccine preparation is time-consuming and technically challenging. Here the hGM-CSF-engineered K-562 cell line was constructed to simplify tumor vaccine preparation process. Methods The eukaryocyte expressing plasmid pcDNA3.1/GM-CSF was first constructed and its accuracy was verified through sequencing. The pcDNA3.1/GM-CSF was transfected into COS-7 cells to verify GM-CSF expression and cytokine activity using TF-1 cell line. Then the plasmid was transfected into K-562 cell line using liposome method, and was selected under G-418 and sub-cloned by limiting dilution. GM-CSF product from the monoclone GM-CSF-K-562 cell lines was quantified using ELISA method. Results We successfully constructed the hGM-CSF eukaryocyte expressing plasmid and hGM-CSF expressing K-562 cell line. Conclusion The construction of K-562/GM-CSF line will simplify the preparation of tumor vaccine, thus facilitating the application of tumor vaccination therapy in clinical application.
文摘The CD4+/CD56+ hematodermic neoplasm is a rare aggressive systemic neoplasm for which effective therapies have not yet been established, it is clinically characterized by cutaneous involvement with spread to bone marrow, blood and poor prognosis with current chemotherapy regimens. Our objective is to report diagnosis and treatment difficulties of CD4+/CD56+ hematodermic neoplasm. We describe here a Tunisian man who presented with subcutaneous ulcerated lesion localized in the right leg and multiples generalized nodules. Skin biopsy showed an atypical lymphoid cell infiltration with an angiocentric pattern and extensive necrosis by immuno-histochemical analysis, these cells were positive for CD4, CD56, granzyme B and negative for CD8, CD123, CD20 and CD30. T-cell rearrangement and Epstein-Barr-virus (EBV) in situ hybridation studies were negative. The patient underwent 5 cycles chemotherapy SMILE regimen monthly sandwiched with radiotherapy on the residual lesions of the right leg with great tolerance but he relapsed within 8months with skin, blood, bone marrow, lung, and cerebrospinal involvement. Based on these findings, the patient was diagnosed with CD4+/CD56+ hematodermic neoplasm (blastic NK-like T-cell lymphoma) treated with one course of hyper-CVAD regimen, he died within 20 days with a septic chok. Despite the use of L-Asparaginase and radiotherapy the prognosis is very poor;we suggest the exploration for highly active drugs, hematopoietic stem cell transplantation (HSCT) is crucial to improve survival.
文摘Sickle cell disease is an autosomal recessive genetic disease. Vaso occlusive crisis (VOC) is frequently seen in such patients. Painful VOC is usually recurrent, of variable severity due to many factors and its management poses important challenge in the clinical practice. Few patients do not respond to standard therapies and continue to suffer severe pain for prolonged period or land to serious life threatening situation. The red cell exchange by aphaeresis is presumed to be one efficient alternative in this situation which can reduce the level of HbS below 40% - 50%. However, it is costly and not available everywhere. Both circumstances are common in our state where incidence of sickle cell disease is quite high. In such situations simple red cell exchange i.e. removing 1 unit (350 ml) of blood manually (by phlebotomy) and replacement with one unit normal red cell is effective. All of our four cases of SCA with severe acute VOC, are not responding to standard therapy but responded efficiently to this simple red cell exchange transfusion. Our present observation may pave the way of one simple, affordable, and effective measure to reduce the pain of severe acute VOC not responding to standard therapy. Moderate reduction of HbS by 8% - 14% by simple red cell exchange transfusion was associated with relief of pain of acute VOC;a new observation was reported in all our 4 cases which need to be validated by larger controlled studies.
文摘Background and Aim: Primary testicular lymphoma (PTL) is a rare form of extranodal non-Hodgkin’s lymphoma. It represents for 1% - 2% of non-Hodgkin’s lymphoma, and mostly affects the elderly. We describe an interesting case of PTL managed by a combined multimodal approach with a review of the literature. Case Presentation: Patient aged 56 years, consulted for an increase in the volume of the right testicle without associated pain, all evolving in the context of a slight decline in general condition. Clinical examination revealed a large painless mass in the right scrotal bursa. A scrotal ultrasound showed a right intra-testicular mass. The patient had undergone inguinal orchiectomy. Pathological analysis showed diffuse large B-cell lymphoma of the testis. Whole-body 18-fluorodeoxyglucose positron emission tomography (18-FDG-PET-CT) showed no suspicious hypermetabolism. Lumbar puncture did not reveal malignant cells in the cerebrospinal fluid (CSF). The patient then received 6 cycles of chemotherapy according to the R-CHOP protocol (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone) and 2 cycles of intrathecal methotrexate. After chemotherapy, scrotal radiotherapy at a dose of 30 Gy was delivered. The evolution was marked by the death of the patient six months after the end of the scrotal radiotherapy following a diffuse lymph node relapse with a profound alteration of the general state. Conclusion: The treatment depends imperatively on the stage of the disease. The therapeutic approach is multimodal and combined based on orchiectomy, systemic and intrathecal treatment and scrotal radiotherapy. PTL is an aggressive malignant with a poor prognosis. Randomized trials are needed to define a better therapeutic strategy.
文摘Objective:To evaluate coagulation abnormalities and their relationship with bleeding manifestations among patients with dengue.Methods:This observational study was conducted on 292 adult dengue patients who were admitted to a tertiary care hospital of Western India from July 2021 to June 2022.Coagulation tests including prothrombin time(PT),international normalized ratio(INR),activated partial thromboplastin time(aPTT),fibrinogen,and D-dimer were performed.Patients were monitored for bleeding manifestations.Results:Coagulation abnormalities were reported in 42.8%of the patients.Overall,prolonged aPTT was the most common coagulation abnormality(40.8%),followed by low fibrinogen(38.7%),raised D-dimer(31.2%),raised INR(26.0%)and prolonged PT(19.2%).Bleeding manifestations were present in 19.9%patients.PT,INR,aPTT and D-dimer levels were significantly higher(P<0.01)and fibrinogen level was significantly lower(P<0.001)in patients with bleeding compared to patients without bleeding.Patients with bleeding had a significantly higher rate of all coagulation abnormalities than patients without bleeding(P<0.01).Conclusions:Patients with bleeding showed a significantly higher frequency of coagulation abnormalities compared to patients without bleeding.Patients with dengue should be assessed for coagulation abnormalities.
文摘AIM: To assess the effect of Helicobacter pylori (H. pylori) eradication on platelet counts in patients with chronic immune thrombocytopenic purpura (cITP).
文摘The acquisition of secondary chromosomal aberrations in chronic myeloid leukemia (CML) patients with Philadelphia chromosome-positive (Ph+) karyotype signifies clonal evolution associated with the progression of the disease to its accelerated or blastic phase. Therefore, these aberrations have clinical and biological significance. T(3;12)(q26;p13), which is a recurrent chromosomal aberration observed in myeloid malignancies, is typically associated with dysplasia of megakaryocytes, multilineage involvement, short duration of any blastic phase, and extremely poor prognosis. We have identified a recurrent reciprocal translocation between chromosomes 3 and 12 with different breakpoint at bands 3q21 in the malignant cells from a 28-year-old man. The patient was initially diagnosed as having Ph+ CML in the chronic phase. The t(3;12)(q21;p13) translocation occurred 4 years after the patient was first diagnosed with CML while undergoing tyrosine kinase inhibitor therapy. We confirmed the t(3;12)(q21;p13) translocation via fluorescence in situ hybridization assay by using whole-chromosome paint probes for chromosomes 3 and 12. Our findings demonstrate that, similar to other recurrent translocations involving 3q26 such as t(3;3) and t(3;21), the t(3;12)(q21;p13) translocation is implicated not only in myelodysplastic syndrome and acute myeloid leukemia but also in the progression of CML. These findings extend the disease spectrum of this cytogenetic aberration.
文摘Dasatinib is a second-line tyrosine kinase inhibitor used in patients with imatinib resistant or intolerant chronic myeloid leukemia (CML) and Philadelphia chromosomepositive acute leukemia. Gastrointestinal bleeding may occur in up to 7% of patients using dasatinib, although, severe dasatinib-related acute colitis had rarely been reported. Here, we present the case of a 36-year-old female who progressed to acute myeloid leukemia after fourteen months of receiving imatinib for CML in the chronic phase and was treated with a dasatinib-containing chemotherapy regimen. On day 34 of treatment, the patient developed moderate abdominal pain and bloody diarrhea with mucous. Analyses of stool specimens were negative for parasites, Clostridium difficile , and other pathogenic bacteria. The cytomegalovirus pp65 antigen was negative in her blood leukocytes. A colonoscopy revealed acute colitis, and a mucosal biopsy showed nonspecific colitis. The patient was treated with broad-spectrum antibiotics, bowel rest and hydration, and dasatinib treatment was stopped. Her bloody diarrhea improved within 72 h. After confirming cytological remission, the patient received initial course of consolidation, and dasatinib treatment was reinstated. However, hemorrhagic colitis recurred. After discontinuing dasatinib, herhemorrhagic colitis drastically improved and did not recur following the administration of nilotinib. The characteristics of our patient suggest that dasatinib treatment can lead to hemorrhagic colitis, which typically resolves after discontinuation of the drug.
文摘Background: The role of human multidrug resistance gene (MDR1) SNPs in the interindividual variability of imatinib mesylate (IM) response has received considerable attention. We aimed to study the association between SNPs of the MDR1 gene (C1236T, G2677T/A, C3435T) and IM response in chronic myeloid leukemia (CML) patients. Method: A retrospective case-control study was conducted on 48 patients with CML undergoing IM therapy. All patients were genotyped using PCR-RFLP method. Results: The genotype and allele frequencies of C1236T and C3435T were not significantly different between CML patients responders and non-responders to IM (p > 0.05). The frequencies of 2677T allele and 2677TT genotype were significantly increased in CML patients IM responders which as compared with IM non-responders (50% vs 26.9%, p = 0.013 and 27.3% vs 3.8%, p = 0.029 respectively). Whereas the 2677AA genotype and CAC haplotype were found only in CML patients IM non-responders (15.4%). Conclusion: Pretreatment genotyping of G2677A/T appears to be useful for predicting IM resistance, which may allow the best choice of drug treatment for CML patients.
文摘Background Myelodysplastic syndromes (MDSs), also called preleukemias, are a group of myeloid hematopoietic malignant disorders. We studied the transformation of MDS into acute myeloid leukemia (AML).Methods Leukemic transformation in 151 patients with MDS was dynamically followed up. The clinical manifestation, peripheral blood and bone marrow condition, karyotypes, immunophenotypes, response to treatment, and prognosis of AML evolution from MDS (MDS-AML) were also observed.Results During the course of this study, over the past eight years and seven months, 21 (13.91%) of 151 MDS patients progressed to overt leukemia, with a median interval of 5 (1-23) months. There were no significant differences between rates of leukemic transformation in comparison with the refractory anemia (RA), RA with excess of blasts (RAEB), and RAEB in transformation (RAEB-t) patient groups. Transformation occurred either gradually or rapidly. There were five parameters positively correlated to leukemic transformation: under 40 years of age, pancytopenia of 3 lineages, more than 15% blasts in the bone marrow, at least two abnormal karyotypes, and treatment with combined chemotherapy. All of the 21 patients with leukemia suffered from MDS-AML, and most of them were M 2, M 4, or M 5. Two (9.52%) MDS-AML patients developed extramedullary infiltration. Leukopenia was found in 47.62% of these patients. Two thirds of these patients, whose bone marrows were generally hypercellular, suffered from neutropenia. After developing AML, 8 (47.06%) patients developed abnormal karyotypes. High expression of immature myeloid antigens, including CD 33 [(49.83±24.50)%], CD 13 [(36.38±33.84)%], monocytic antigen CD 14 [(38.50±24.60)%], and stem cell marker CD 34 [(34.67±30.59)%], were found on bone marrow mononuclear cells from MDS-AML patients after leukemic transformation. In some cases, lymphoid antigens, such as CD 5, CD 7, CD 9, and CD 19, coexisted with myeloid antigens. A low complete remission rate (31.25%) and a short survival time, with median survival of 6 (1-28) months, were found in patients with MDS-AML treated by induction chemotherapy.Conclusions MDS has a high risk of developing into AML, either gradually or rapidly. Patients with MDS-AML have specific biological characteristics and a worse prognosis.
